Depletion of serotonin in the nervous system of Aplysia reduces the behavioral enhancement of gill withdrawal as well as the heterosynaptic facilitation produced by tail shock

Abstract

Noxious stimuli, such as electrical shocks to the animal's tail, enhance Aplysia's gill- and siphon-withdrawal reflex. Previous experimental work has indicated that this behavioral enhancement, known as dishabituation (if the reflex has been habituated) or sensitization (if it has not been habituated), might be mediated, at least in part, by the endogenous monoaminergic transmitter serotonin (5-HT). To assess 5-HT's role in dishabituation and sensitization of Aplysia withdrawal reflex, we treated Aplysia with the serotonergic neurotoxin 5,7-dihydroxytryptamine (5,7-DHT). We found that 5,7-DHT treatment significantly reduced the dishabituation of the withdrawal reflex produced by tail shock. Treatment with the neurotoxin also blocked the heterosynaptic facilitation of monosynaptic connections between siphon sensory neurons and their follower cells, which contributes to the behavioral enhancement. Analysis by high-performance liquid chromatography indicated that 5,7-DHT treatment significantly reduced 5-HT levels in the Aplysia CNS. Moreover, the neurotoxic effects of 5,7-DHT appeared to be relatively specific for serotonergic pathways. Thus, 5,7-DHT treatment did not disrupt the ability of nonserotonergic facilitatory interneurons, the L29 cells, to facilitate the connections of siphon sensory neurons. Also, 5,7-DHT reduced 5-HT-dependent, but not dopamine-dependent, histofluorescence in Aplysia central ganglia. Finally, 5,7-DHT does not reduce the levels of the facilitatory peptides SCPA and SCPB within the Aplysia CNS. Our results, together with those of Mackey et al. (1989), indicate that 5-HT plays a major role in mediating dishabituation and sensitization of Aplysia's withdrawal reflex.

Serotonin Depletion Does Not Prevent Intrinsic Sensitization in the Leech

“…Intrinsic sensitization of S T -elicited shortening was equally inducible in both control and 5-HT-depleted leeches. These results suggest that intrinsic sensitization of leech shortening is a 5-HT-independent process, unlike extrinsic sensitization and dishabituation of shortening in the leech (Ehrlich et al 1992;Sahley 1994) or dishabituation of gill withdrawal in Aplysia (Glanzman et al 1989), both of which are disrupted by 5-HT-depletion. Another interesting result from these experiments was that 5-HT depletion altered the habituation process in S N -elicited behavior that normally occurs following habituation training at the S T .…”

“…In the leech, depletion of serotonin (5-HT) from the R cells using the 5-HT analog, 5,7-dihydroxytryptamine (5,7-DHT), prevents sensitization of the whole-body shortening response (Ehrlich et al 1992;Sahley 1994). In Aplysia, 5,7-DHT-induced 5-HT depletion disrupts dishabituation and prevents the heterosynaptic facilitation produced by dishabituating stimuli (both sensitization and dishabituation are produced by the same noxious stimulus) (Glanzman et al 1989). Assuming that 5-HT-dependent sensitization is extrinsic in nature, it is reasonable to hypothesize that intrinsic sensitization should not be affected by manipulations that disrupt extrinsic sensitization.…”

Pairing-specific, activity-dependent presynaptic facilitation at Aplysia sensory-motor neuron synapses in isolated cell culture

“…Three different transmitters contribute to the presynaptic facilitation induced by tail shock: 5-HT, small cardioactive peptide (SCP), and the as yet unidentified transmitter released by the L29 group of modulatory interneurons (Brunelli et al, 1976;Hawkins et al, 1981;Abrams et al, 1984;Glanzman et al, 1989;Mackey et al, 1989;Mercer et al, 199 1). The most extensively studied of these is 5-HT, which facilitates release from sensory neurons by two different processes.…”

FMRFamide produces biphasic modulation of the LFS motor neurons in the neural circuit of the siphon withdrawal reflex of Aplysia by activating Na+ and K+ currents

“…These changes in the sensory neuron to motor neuron synaptic connections in response to tail shock are largely due to presynaptic changes. The primary facilitatory transmitter released by tail shock is 5-HT (Glanzman et al, 1989;Hawkins, 1989;Mackey et al, 1989;Mercer et al, 199 1). 5-HT's facilitatory effects on the presynaptic sensory neurons include a decrease in spike threshold, spike broadening, and an increase in transmitter release (Brunelli et al, 1976;Castellucci and Kandel, 1976;Klein and Kandel, 1980;Walters et al, 1983;Klein et al, 1986;Dale and Kandel, 1990).…”